雌激素及其受体通过经典的 ER 途径影响 MMP2 和 MMP9 的表达，促进下肢静脉血管平滑肌细胞的迁移。
Estrogen and estrogen receptor affects MMP2 and MMP9 expression through classical ER pathway and promotes migration of lower venous vascular smooth muscle cells.
机构信息
Department of Vascular Surgery, Intensive Care Unit, and Department of Anesthesiology; The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China.
出版信息
Eur Rev Med Pharmacol Sci. 2020 Feb;24(3):1460-1467. doi: 10.26355/eurrev_202002_20205.
OBJECTIVE
To explore the role of estrogen and estrogen receptors in the migration of vascular smooth muscle cells in varicose lower-extremity veins.
PATIENTS AND METHODS
Tissue samples of normal lower extremity vein (56 cases) and varicose lower extremity vein (47 cases) were collected. Western blot and real-time fluorescent qPCR were performed to measure the expression of Estrogen receptor α (ERα) in tissues. Two cell co-culture systems were established for human umbilical vein endothelial cells (HUVECs) and human umbilical vein smooth muscle cells (HUVSMCs). One system was incubated under normal oxygen conditions (normal oxygen group), and the other was under oxygen-poor conditions (hypoxia group). The two systems were treated with 10-7 mM Estrogen E2, 10-7 mM BSA-conjugated Estrogen E2-BSA, 10-7 mM Estrogen E2+10-3 mM Tamoxifen (TAM), respectively for 24 h. The treated cells were subjected to cell scratch assay, transwell assay, and Western blot analysis of MMP2 and MMP9 protein expression.
RESULTS
The expression of ERα in varicose lower extremity vein was significantly up-regulated compared with that in normal lower extremity vein. The cell migration rate and the number of migrating cells in untreated hypoxia group and E2-treated normal oxygen group were comparable (p>0.05) to those in untreated normal oxygen group. The cell migration rate and the number of migrating cells were significantly increased (p<0.05) in E2-treated hypoxia group, compared with E2-treated normal oxygen group and untreated hypoxia group. The cell migration rate, the number of migrating cells, and expression levels of MMP2 and MMP9 were significantly decreased in E2/TAM-treated hypoxia group, compared with those in E2-treated hypoxia group.
CONCLUSIONS
In summary, E2 can promote the migration of vascular smooth muscle cells and induce varicose veins of the lower extremities, which may be related to the promotion of MMP2 and MMP9 expression through the classical pathway of ER.
目的
探讨雌激素及其受体在下肢静脉曲张血管平滑肌细胞迁移中的作用。
患者与方法
收集正常下肢静脉（56 例）和静脉曲张下肢静脉（47 例）组织标本。采用 Western blot 和实时荧光定量 PCR 检测组织中雌激素受体α（ERα）的表达。建立人脐静脉内皮细胞（HUVECs）和人脐静脉平滑肌细胞（HUVSMCs）的两种细胞共培养系统。一组在常氧条件下孵育（常氧组），另一组在低氧条件下孵育（低氧组）。两组均分别用 10-7 mM 雌激素 E2、10-7 mM BSA 偶联雌激素 E2-BSA、10-7 mM 雌激素 E2+10-3 mM 他莫昔芬（TAM）处理 24 h。划痕实验、Transwell 实验和 Western blot 分析 MMP2 和 MMP9 蛋白表达。
结果
与正常下肢静脉相比，静脉曲张下肢静脉中 ERα 的表达明显上调。未经处理的低氧组和未经处理的常氧组 E2 处理组的细胞迁移率和迁移细胞数无明显差异（p>0.05），与未经处理的常氧组相比。E2 处理的低氧组细胞迁移率和迁移细胞数明显增加（p<0.05），与 E2 处理的常氧组和未经处理的低氧组相比。E2/TAM 处理的低氧组细胞迁移率、迁移细胞数和 MMP2、MMP9 的表达水平明显低于 E2 处理的低氧组。
结论
总之，E2 可促进血管平滑肌细胞的迁移，诱导下肢静脉曲张，这可能与通过经典途径 ER 促进 MMP2 和 MMP9 表达有关。
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